Medical imaging is a well-established technique (in the field of equipments for medical applications), which allows analyzing a body part of a patient in a substantially non-invasive manner. A specific medical imaging technique is based on the administration of an ultrasound contrast agent (UCA) to the patient (for example, consisting of a suspension of phospholipid-stabilized gas-filled microbubbles); the contrast agent acts as an efficient ultrasound reflector, so that it can be easily detected by applying ultrasound waves and measuring a resulting echo signal. The echo signal so obtained may be used to estimate different physiologic characteristics of the body part; for example, as the contrast agent flows at the same velocity as the blood in the patient, its tracking provides a representation of a perfusion of the blood in the body part (from which it is possible to derive haemodynamic and/or morphological information about the body part).
Target-specific contrast agents, adapted to reach a specific (biological) target and then remain immobilized thereon, have also been proposed in the last years for characterizing and facilitating the detection of specific pathologies. Particularly, a target-specific contrast agent is capable of attaching to the corresponding target—such as particular tissues or receptors—by means of a specific interaction therewith; for example, the desired behavior may be achieved by incorporating a target-specific ligand (e.g., capable of interacting with inflammatory or tumoral tissues) in the formulation of the contrast agent. In addition, contrast agents may also be conveyed or accumulated to a specific location, such as tissues or organs, by means of a non-specific interaction therewith; for example, the contrast agent may be recognized as a foreign substance by the immune system of the patient and then transported to the liver for its metabolism and elimination. In any case, the detection and the quantification of the above-mentioned targeted contrast agent immobilized on the desired target (either with specific or non-specific interaction) provides valuable information about the presence, quantity, functionality, and spatial distribution of the target; for example, this information may allow distinguishing pathologies that would be otherwise difficult to identify.
However, the detection and quantification of the immobilized contrast agent may be hindered by the fact that only a relatively small fraction of the total amount of the targeted contrast agent actually reaches the target and remains immobilized thereon; most of the targeted contrast agent continues instead to circulate for quite a long time (e.g., several minutes)—for example, until it is filtered out by the lungs and/or in the liver of the patient. The echo signal that is measured is then the result of both a contribution of the immobilized targeted contrast agent and a contribution of the circulating or free-flowing targeted contrast agent. Therefore, it may be quite difficult to extract from this echo signal the desired information about the immobilized contrast agent (so as to detect and quantify it).
A solution known in the art that tackles this problem is disclosed in “Albumin Microbubble Persistence During Myocardial Contrast Echocardiography Is Associated With Microvascular Endothelial Glycocalyx Damage”—Jonathan R. Lindner, Suad Ismail, William D. Spotnitz, Danny M. Skyba, Ananda R. Jayaweera and Sanjiv Kaul—Circulation 1998; 98; 2187-2194 by American Heart Association. 7272 Greenville Avenue, Dallas, Tex. 72514—Print ISSN: 0009-7322. Online ISSN: 1524-4539, which is incorporated by reference. Particularly, this document proposes fitting the echo signal by a mathematical model that consists of the weighted sum of a γ-variate function (modeling the circulation of the contrast agent) and the integral of the same γ-variate (representing the fraction of the targeted contrast agent that immobilizes).
However, the solution described in the above listed document may be unsatisfactory. Indeed, experimental results have shown that the obtained results do not correctly represent the actual rate of the immobilization of the contrast agent. Therefore, it may not be possible to detect and quantify the immobilized contrast agent with an acceptable degree of accuracy. This prevents the clinical application of the known analysis techniques based on the use of targeted contrast agents.